Pulmonary Embolism: Difference between revisions

[[File:Pulmonary embolism scintigraphy PLoS.png|thumb|Ventilation-perfusion scintigraphy in a woman taking hormonal contraceptives and valdecoxib.<br/>(A) After inhalation of 20.1 mCi of Xenon-133 gas, scintigraphic images were obtained in the posterior projection, showing uniform ventilation to lungs.<br/>

CT pulmonary angiography (CTPA) is a pulmonary angiogram obtained using computed tomography (CT) with radiocontrast rather than right heart catheterization. Its advantages are clinical equivalence, its non-invasive nature, its greater availability to patients, and the possibility of identifying other lung disorders from the differential diagnosis in case there is no pulmonary embolism. Assessing the accuracy of CT pulmonary angiography is hindered by the rapid changes in the number of rows of detectors available in multidetector CT (MDCT) machines. <cite>REFNAME16</cite> According to a cohort study, single-slice spiral CT may help diagnose detection among patients with suspected pulmonary embolism. <cite>REFNAME17</cite> In this study, the sensitivity was 69% and specificity was 84%. In this study which had a prevalence of detection was 32%, the positive predictive value of 67.0% and negative predictive value of 85.2% ([http://medinformatics.uthscsa.edu/calculator/calc.shtml?calc_dx_SnSp.shtml?prevalence=32&sensitivity=69&specificity=84 click here] to adjust these results for patients at higher or lower risk of detection). However, this study's results may be biased due to possible incorporation bias, since the CT scan was the final diagnostic tool in patients with pulmonary embolism. The authors noted that a negative single slice CT scan is insufficient to rule out pulmonary embolism on its own. A separate study with a mixture of 4 slice and 16 slice scanners reported a sensitivity of 83% and a specificity of 96%. This study noted that additional testing is necessary when the clinical probability is inconsistent with the imaging results. <cite>REFNAME18</cite> CTPA is non-inferior to VQ scanning, and identifies more emboli (without necessarily improving the outcome) compared to VQ scanning. <cite>Anderson2007</cite>

''Ventilation/perfusion scan'' (or ''V/Q scan'' or ''lung scintigraphy''), which shows that some areas of the lung are being ventilated but not perfused with blood (due to obstruction by a clot). This type of examination is used less often because of the more widespread availability of CT technology, however, it may be useful in patients who have an allergy to iodinated contrast or in pregnancy due to lower radiation exposure than CT. <cite>REFNAME19</cite>

*''Chest X-rays'' are often done on patients with shortness of breath to help rule-out other causes, such as congestive heart failure and rib fracture. Chest X-rays in PE are rarely normal, <cite>REFNAME20</cite> but usually lack signs that suggest the diagnosis of PE (e.g. Westermark sign, Hampton's hump).

*''Ultrasonography of the legs'', also known as ''leg doppler'', in search of deep venous thrombosis (DVT). The presence of DVT, as shown on ultrasonography of the legs, is in itself enough to warrant anticoagulation, without requiring the V/Q or spiral CT scans (because of the strong association between DVT and PE). This may be valid approach in pregnancy, in which the other modalities would increase the risk of birth defects in the unborn child. However, a negative scan does not rule out PE, and low-radiation dose scanning may be required if the mother is deemed at high risk of having pulmonary embolism. {{Citation needed|date=August 2011}}

[[File:Pulmonary embolism ECG.jpg|thumb|Electrocardiogram of a patient with pulmonary embolism showing sinus tachycardia of approximately 150 beats per minute and right bundle branch block.]]

An electrocardiogram (ECG) is routinely done on patients with chest pain to quickly diagnose myocardial infarctions (heart attacks). An ECG may show signs of right heart strain or acute ''cor pulmonale'' in cases of large PEs - the classic signs are a large S wave in lead I, a large Q wave in lead III and an inverted T wave in lead III ("S1Q3T3"). <cite>McGinn</cite> This is occasionally (up to 20%) present, but may also occur in other acute lung conditions and has therefore limited diagnostic value. The most commonly seen signs in the ECG is sinus tachycardia, right axis deviation and right bundle branch block. <cite>REFNAME21</cite>  Sinus tachycardia was however still only found in 8 - 69% of people with PE. <cite>REFNAME22</cite>

In massive and submassive PE, dysfunction of the right side of the heart can be seen on echocardiography, an indication that the pulmonary artery is severely obstructed and the heart is unable to match the pressure. Some studies (see below) suggest that this finding may be an indication for thrombolysis. Not every patient with a (suspected) pulmonary embolism requires an echocardiogram, but elevations in cardiac troponins or brain natriuretic peptide may indicate heart strain and warrant an echocardiogram. <cite>REFNAME23</cite>

In most cases, anticoagulant therapy is the mainstay of treatment. Acutely, supportive treatments, such as oxygen or analgesia, are often required.

In most cases, anticoagulant therapy is the mainstay of treatment. Heparin, low molecular weight heparins (such as enoxaparin and dalteparin), or fondaparinux is administered initially, while warfarin, acenocoumarol, or phenprocoumon therapy is commenced (this may take several days, usually while the patient is in the hospital). Low molecular weight heparin may reduce bleeding among patients with pulmonary embolism as compared to heparin according to a systematic review of randomized controlled trials by the Cochrane Collaboration. <cite>REFNAME28</cite> The relative risk reduction was 40.0%. For patients at similar risk to those in this study (2.0% had bleeding when not treated with low molecular weight heparin), this leads to an absolute risk reduction of 0.8%. 125.0 patients must be treated for one to benefit.

It is possible to treat low risk patients (risk class I or class II) as outpatients. <cite>Aujesky2011</cite>  A randomised trial of 344 patients (171 outpatients and 168 inpatients) found that outcomes were equivalent whether patients were treated in hospital or at home (there was one death at 90 days in each group). <cite>Aujesky2011</cite> <cite>Aujesky2007</cite> This confirms the findings of an earlier systematic review of observational studies. <cite>REFNAME29</cite>

Warfarin therapy often requires frequent dose adjustment and monitoring of the INR. In PE, INRs between 2.0 and 3.0 are generally considered ideal. If another episode of PE occurs under warfarin treatment, the INR window may be increased to e.g. 2.5-3.5 (unless there are contraindications) or anticoagulation may be changed to a different anticoagulant e.g. low molecular weight heparin. In patients with an underlying malignancy, therapy with a course of low molecular weight heparin may be favored over warfarin based on the results of the CLOT trial. <cite>REFNAME30</cite>

Similarly, pregnant women are often maintained on low molecular weight heparin to avoid the known teratogenic effects of warfarin, especially in the early stages of pregnancy. {{Citation needed|date=August 2011}}

Warfarin therapy is usually continued for 3–6 months, or "lifelong" if there have been previous DVTs or PEs, or none of the usual risk factors is present. An abnormal D-dimer level at the end of treatment might signal the need for continued treatment among patients with a first unprovoked pulmonary embolus. <cite>REFNAME32</cite>

Massive PE causing hemodynamic instability (shock and/or hypotension, defined as a systolic blood pressure <90 mmHg or a pressure drop of 40 mmHg for>15 min if not caused by new-onset arrhythmia, hypovolemia or sepsis) is an indication for thrombolysis, the enzymatic destruction of the clot with medication. It is the best available medical treatment in this situation and is supported by clinical guidelines. <cite>REFNAME33</cite> <cite>ESC</cite> <cite>REFNAME34</cite>

The use of thrombolysis in non-massive PEs is still debated. The aim of the therapy is to dissolve the clot, but there is an attendant risk of bleeding or stroke. <cite>REFNAME35</cite> The main indication for thrombolysis is in submassive PE where right ventricular dysfunction can be demonstrated on echocardiography, and the presence of visible thrombus in the atrium. <cite>REFNAME36</cite>

Surgical management of acute pulmonary embolism (pulmonary thrombectomy) is uncommon and has largely been abandoned because of poor long-term outcomes. However, recently, it has gone through a resurgence with the revision of the surgical technique and is thought to benefit selected patients. <cite>REFNAME37</cite>

Chronic pulmonary embolism leading to pulmonary hypertension (known as ''chronic thromboembolic hypertension'') is treated with a surgical procedure known as a pulmonary thromboendarterectomy.

If anticoagulant therapy is contraindicated and/or ineffective, or to prevent new emboli from entering the pulmonary artery and combining with an existing blockage, an inferior vena cava filter may be implanted. <cite>REFNAME38</cite>

Mortality from untreated PE is said to be 26%. This figure comes from a trial published in 1960 by Barrit and Jordan <cite>Barritt</cite>, which compared anticoagulation against placebo for the management of PE. Barritt and Jordan performed their study in the Bristol Royal Infirmary in 1957. This study is the only placebo controlled trial ever to examine the place of anticoagulants in the treatment of PE, the results of which were so convincing that the trial has never been repeated as to do so would be considered unethical. That said, the reported mortality rate of 26% in the placebo group is probably an overstatement, given that the technology of the day may have detected only severe PEs.

Prognosis depends on the amount of lung that is affected and on the co-existence of other medical conditions; chronic embolisation to the lung can lead to pulmonary hypertension. After a massive PE, the embolus must be resolved somehow if the patient is to survive. In thrombotic PE, the blood clot may be broken down by fibrinolysis, or it may be organized and recanalized so that a new channel forms through the clot. Blood flow is restored most rapidly in the first day or two after a PE. <cite>REFNAME39</cite> Improvement slows thereafter and some deficits may be permanent. There is controversy over whether or not small subsegmental PEs need to be treated at all <cite>REFNAME40</cite> and some evidence exists that patients with subsegmental PEs may do well without treatment. <cite>REFNAME41</cite> <cite>REFNAME42</cite>

After a first PE, the search for secondary causes is usually brief. Only when a second PE occurs, and especially when this happens while still under anticoagulant therapy, a further search for underlying conditions is undertaken. This will include testing ("thrombophilia screen") for Factor V Leiden mutation, antiphospholipid antibodies, protein C and S and antithrombin levels, and later prothrombin mutation, MTHFR mutation, Factor VIII concentration and rarer inherited coagulation abnormalities. {{Citation needed|date=August 2011}}